Cholesterol enhances contractile responses in isolated small mesenteric arteries of normotensive and spontaneously hypertensive rats

Objective In order to examine possible mechanisms by which hypercholesterol emia may contribute to the development of cardiovascular disease, we invest igated the effect of cholesterol enrichment on contractility in isolated sm all rat mesenteric arteries. Design Contractile responses of cholesterol-enriched isolated small mesente ric arteries of normotensive Wistar-Kyoto (WKY) rats and spontaneously hype rtensive rats (SHR) were compared with control groups. Methods First- to second-order mesenteric arteries (327-349 mu m internal l umen diameter) were dissected from the mesenteric bed of 10-20-week-old mal e WKY rats and SHR, and incubated in cholesterol-free and cholesterol-rich (150 mu g/ml) medium. Isolated arteries were mounted on a Mulvany-Halpern m yograph for measurement of isometric tension. Results Cholesterol significantly increased active wall tension and active wall pressure in WKY rat arteries and active wall tension in SHR arteries i n response to potassium chloride, norepinephrine and serotonin (P < 0.05). In addition, contractile responses to all agonists were significantly highe r in cholesterol-enriched SHR arteries compared with cholesterol-enriched W KY rat vessels (P < 0.05). Conclusions These findings suggest that elevated cholesterol content enhanc es agonist-stimulated contractility in small mesenteric resistance arteries , providing a possible mechanism by which hypercholesterolemia may contribu te to the development of hypertension. (C) Lippincott Williams & Wilkins.